Potassium Carbonate → HCID 66838605, compound

HRID 1752352Notes

Reaction equation

HRID 1752352 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([OH:29])=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[Cl:15].CS(O[CH:35]1[CH2:49][C@@H:38]2[CH2:39][N:40]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:41][C@@H:37]2[CH2:36]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C.CO.C(OCC)(=O)C>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:29][CH:35]4[CH2:49][C@@H:38]5[CH2:39][N:40]([C:42]([O:44][C:45]([CH3:47])([CH3:46])[CH3:48])=[O:43])[CH2:41][C@@H:37]5[CH2:36]4)=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[Cl:15]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 58293778HCID 58293778, compoundHCID 136335147HCID 136335147, compound

Product 1

HCID 66838605HCID 66838605, compoundYield 98%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of 4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-ol trifluoroacetate (salt) (0.22 g, 0.49 mmol), 1,1-dimethylethyl(3aR,6aS)-5-{[(methylsulfonyl)oxy]}hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (0.15 g, 0.45 mmol), potassium carbonate (0.34 g, 2.50 mmol) in N,N-dimethylacetamide (5 mL) was heated in a sealed reaction tube at 90° C. for 12 h. The crude reaction mixture was diluted with 100 mL 10% methanol in ethyl acetate and washed with saturated aqueous sodium bicarbonate (1×30 mL), water (1×30 mL) and brine (1×30 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. Column chromatography (SiO2, 3:2 hexanes:acetone) provided 1,1-dimethylethyl(3aR,6aS)-5-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy})hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (0.23 g, 98%). 1H NMR (400 MHz, d6-DMSO): 9.57 (s, 1H), 8.52 (s, 1H), 8.24 (d, 1H), 7.88 (dd, 1H), 7.78 (s, 1H), 7.62 (d, 1H), 7.13 (s, 1H), 5.15 (m, 1H), 3.96 (s, 3H), 3.42 (m, 2H), 3.36 (m, 2H), 2.80 (bs, 2H), 2.06 (m, 2H), 1.94 (m, 2H), 1.40 (s, 9H). MS (EI) for C27H30Cl2N4O4: 547 (MH+).

Workup

  1. customThe crude reaction mixture
  2. washwashed with saturated aqueous sodium bicarbonate (1×30 mL), water (1×30 mL) and brine (1×30 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-527d7d6d0e3345d0832593db6ea08d24
Source dataset
uspto-grants-2015_10
Patent number
US09163006B2

Reaction notes

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